E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aortic stenosis |
Aortastenose |
|
E.1.1.1 | Medical condition in easily understood language |
Narrowed aortic valve (heart valve) |
Forsnævret aortaklap (hjerteklap) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate in a randomized, double-blinded placebo controlled design if beta-blocker treatment in patients with moderate to severe, asymptomatic AS has beneficial effects on LV myocardial oxidative metabolism, efficiency, contractile function and physical performance. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Aortic valve area <1,2 cm2 and/or transaortic maximal velocity (VmaxAO) of 3,0-5,0 m/s
- Sinus rhythm >60/min after 5 minutes rest
- LVEF >55%
- Male or female
- Age 20-100 years old
- Safe birth control management (intrauterine devices or hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release))
- Negative urine-HCG for women of childbearing potential
- Ability to understand the written patient information and to give informed consent |
|
E.4 | Principal exclusion criteria |
- Systolic BP <100 mmHg after 5 minutes of rest
- Left ventricular posterior wall thickness >17 mm
- Signs or history of myocardial infarction and/or severe ischemic heart disease
- Severe asthma or chronic obstructive pulmonary disease
- New York Heart Association (NYHA) classification > I due to AS
- NYHA > II due to non-cardiac causes
- 2ᵒ or 3ᵒ atrioventricular block
- Ongoing beta-blocker therapy
- Ongoing verapamil or diltiazem therapy
- Ongoing monoamine oxidase inhibitors therapy
- Sick sinus syndrome
- Atrial fibrillation or fluttering
- Lack of stable sinus rhythm
- Pheochromocytoma
- Severe peripheral vascular disease
- Intolerance of metoprolol succinate or its excipients |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and at end of study (22 weeks) |
|
E.5.2 | Secondary end point(s) |
- Myocardial oxygen consumption
- Myocardial perfusion at rest
- LV myocardial function – evaluated by global longitudinal strain, EF and diastolic function
- LVmass
- Aortic valve area and transaortic valve velocities
- 6 minute walking distance
- N-terminal prohormone of brain natriuretic peptide
- Quality of life - estimated by Minnesota living with heart failure questionnaire
- LV wall stress |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and at end of study (22 weeks) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 20 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |